Clinical Review

Systemic Scleroderma: The Truth Beneath a "Skin Disease"

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Skin changes tend to peak within the first five years. Patients who experience them rapidly are at increased risk for severe internal organ involvement.6 With disease progression come facial changes, including a shrunken nose, microglossia, small lips, furrowing around the mouth, telangiectasias, hyperpigmentation (resembling that seen in patients with Addison’s disease), and sclerosis that limits facial expressions, leaving a mask-like appearance.6,10

Calcinosis, the buildup of calcium deposits under the skin, appears in the form of painful, hard nodules, especially in the digits, elbows, knees, and other joints. This occurs in 40% of SSc patients.11 In addition to the already thickened sclerotic skin, calcinosis causes flexion contractures leading to restricted mobility, articular deformities, and dissolution of the distal phalanges.10,16

Noncutaneous Manifestations
In addition to vascular and cutaneous changes, patients affected by SSc may develop a multitude of musculoskeletal complaints, including nonspecific joint pain. These symptoms can manifest as arthritis and cause discomfort in the tendons and muscles. Patients may even develop myopathies and muscle weakness over time.17

GI tract complaints are almost universally seen in patients with SSc; more than 85% of patients experience dysphagia, phagodynia, or other esophageal problems.10 These symptoms usually result from peristaltic abnormalities: reflux, Barrett’s metaplasia, hypomotility, and/or fibrotic strictures. Subsequent complaints may include nausea, vomiting, abdominal pain, and constipation due to colonic hypomotility.18,19 In some patients, malabsorption syndrome can advance to a stage at which parenteral nutrition is required.12

Pulmonary impairment is another common manifestation, affecting possibly 80% to 90% of patients with SSc.2,7 Patients who present with dyspnea or a dry, irritating cough may have underlying lung fibrosis.6,11 Those who report shortness of breath, fatigue, fast heart rates, or blackouts may have pulmonary hypertension, which is seen in one in seven patients.11 Pulmonary hypertension reduces the five-year survival rate from 90% to as low as 50%, making it a significant cause of SSc-related death.10

The most devastating clinical manifestations in SSc patients are renal and heart involvement.20 Among all the possibilities of organ involvement, kidney damage incurs the worst prognosis and the highest mortality. Of patients not treated for this development, only 16% survive longer than one year; with treatment, such patients’ five-year survival is 45%.10

Sclerodermal renal crisis is apparent in patients who meet the diagnostic criteria of proteinuria, azotemia, arterial hypertension, a reduced glomerular filtration rate, hematuria, and microangiopathic hemolytic anemia.20-25 Patients may also present with retrosternal pain, possibly signifying myocardial fibrosis. This complication, in addition to kidney failure, can lead to arrhythmias and ultimately heart failure.

Patient History
Particularly important components of the patient history include gender, race, age, family history, and work environment. Although anyone can develop scleroderma, women are four times more likely than men to develop SSc, and pregnancy increases women’s risk tenfold.11 For unknown reasons, African-Americans are more frequently affected than whites and are at increased risk for serious systemic involvement.4

Symptom onset is most common between ages 25 and 55, although children and elderly persons can be affected.11,26,27

Most research suggests that SSc is not directly inherited, although (as in the case of other autoimmune diseases) genetic factors can predispose people with additional external triggers.21,28,29 A positive family history is a strong risk factor for SSc. In a large cohort-based study, patients with SSc invariably had at least one first-degree relative who was also affected.29

Although the exact cause of SSc remains unknown, substantial research suggests that environmental factors, especially exposure to certain metals and chemical compounds (eg, solvents, pesticides, silica), play a major role in its development.1,16,30 Farmers, factory and construction workers, coal miners, and others may be exposed to these chemicals, so it is important to ask about potentially hazardous occupations.

Physical Examination
Patients in whom any form of scleroderma is suspected should undergo a thorough physical examination. It is here that preliminary signs of internal organ involvement and fibrosis must be detected.

Clinicians should observe the skin for signs of inflammation. Any changes in the skin’s appearance or texture, including tight, hardened, and sclerotic changes of the hands, face, mouth, trunk, and/or digits, should also be noted. The examiner may notice furrowing around the mouth, telangiectasias, and hyperpigmentation.6,10 Signs of vascular damage may be identified, including digital discoloration and ulcers associated with Raynaud’s phenomenon.22

Examination of the skin (with palpation) will reveal information about the disease’s activity, involvement, and severity.31 Active cutaneous disease indicated by inflammatory signs (eg, edema) correlates with active internal disease, such as renal crisis or fibrosing alveolitis.10 Inactive skin disease manifests as sclerotic skin resembling a scar.31

If skin sclerosis is sufficient for suspicion of SSc, additional steps are required. In the ear-nose-throat examination, for example, the mucosal membranes should be observed for signs of Sjögren’s syndrome, since it is associated with SSc.32 The mouth should also be examined for telangiectasias and microglossia.

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